Biotechnology Center, Federal University of Paraíba, João Pessoa, Brazil.
Clin Exp Pharmacol Physiol. 2012 Apr;39(4):373-8. doi: 10.1111/j.1440-1681.2012.05679.x.
In pathological conditions, such as hypertension, there is impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the depressed baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). Male 10-week-old SHR (n = 14) and their controls (Wistar-Kyoto (WKY) rats; n = 14) underwent femoral artery and vein catheterization for conscious blood pressure recording and drug administration. The BRS was obtained by the drug-induced method using phenylephrine (8 μg/kg, i.v.) and sodium nitroprusside (25 μg/kg, i.v.) before and after the administration of tiron (30 mg/kg, i.v.), a superoxide dismutase mimetic, or apocynin (30 μg/kg), an NADPH oxidase inhibitor. Spontaneously hypertensive rats was significantly hypertensive compared with WKY rats (160 ± 7 vs 105 ± 2 mmHg, respectively). However, there was no significant difference in heart rate between the two groups (388 ± 10 vs 370 ± 20 b.p.m.). In addition, SHR exhibited a diminished BRS compared with WKY rats (-1.34 ± 0.11 vs -2.91 ± 0.20 b.p.m./mmHg, respectively). Administration of tiron improved BRS in SHR (from -1.34 ± 0.11 to 2.26 ± 0.21 b.p.m./mmHg), as did apocynin (to -2.14 ± 0.23 b.p.m./mmHg). Serum samples from SHR (n = 20) and WKY rats (n = 20) were collected for thiobarbituric acid-reactive substances assays before and after tiron or apocynin to confirm the reduction in oxidative stress. There was considerably greater oxidative stress in SHR compared with WKY rats (36.2 ± 3.0 vs 13.3 ± 2.6 nmol/L, respectively). Both apocynin and tiron treatment reduced the oxidative stress in SHR (from 36.2 ± 3.0 to 21.5 ± 3.0 nmol/L and from 37.2 ± 3.9 to 21.9 ± 1.6 nmol/L, respectively). The data suggest that acute scavenging of NADPH oxidase-derived superoxide improves baroreflex sensitivity in SHR.
在病理条件下,如高血压,自主血压控制受损导致压力反射敏感性改变。在本研究中,我们假设急性超氧化物清除会恢复自发性高血压大鼠(SHR)的抑郁压力反射敏感性(BRS)。雄性 10 周龄 SHR(n=14)及其对照(Wistar-Kyoto(WKY)大鼠;n=14)接受股动脉和静脉导管插入术,用于清醒血压记录和药物给药。BRS 通过使用苯肾上腺素(8μg/kg,静脉内)和硝普钠(25μg/kg,静脉内)获得,在给予钛(30mg/kg,静脉内),超氧化物歧化酶模拟物或 apocynin(30μg/kg),NADPH 氧化酶抑制剂之前和之后。与 WKY 大鼠相比,自发性高血压大鼠明显高血压(分别为 160±7mmHg 和 105±2mmHg)。然而,两组之间的心率没有显著差异(分别为 388±10bpm 和 370±20bpm)。此外,与 WKY 大鼠相比,SHR 表现出降低的 BRS(分别为-1.34±0.11 bpm/mmHg 和-2.91±0.20 bpm/mmHg)。钛的给药改善了 SHR 的 BRS(从-1.34±0.11 到 2.26±0.21 bpm/mmHg),apocynin 也是如此(至-2.14±0.23 bpm/mmHg)。在给予钛或 apocynin 前后,从 SHR(n=20)和 WKY 大鼠(n=20)收集血清样本进行硫代巴比妥酸反应性物质测定,以确认氧化应激的减少。与 WKY 大鼠相比,SHR 的氧化应激明显更大(分别为 36.2±3.0nmol/L 和 13.3±2.6nmol/L)。apocynin 和钛的治疗均降低了 SHR 的氧化应激(从 36.2±3.0nmol/L 降至 21.5±3.0nmol/L 和从 37.2±3.9nmol/L 降至 21.9±1.6nmol/L)。数据表明,急性清除 NADPH 氧化酶衍生的超氧化物可改善 SHR 的压力反射敏感性。